University of Queensland Diamantina Institute, Brisbane, Queensland, Australia; Translational Research Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria, Australia; Australian Cancer Research Foundation Rational Drug Discovery Centre, St. Vincent's Institute of Medical Research, Fitzroy, VIC, Australia.
Hum Immunol. 2019 May;80(5):281-289. doi: 10.1016/j.humimm.2018.11.002. Epub 2018 Nov 9.
The oxytocinase subfamily of M1 aminopeptidases plays an important role in processing and trimming of peptides for presentation on major histocompatibility (MHC) Class I molecules. Several large-scale genomic studies have identified association of members of this family of enzymes, most notably ERAP1 and ERAP2, with immune-mediated diseases including ankylosing spondylitis, psoriasis and birdshot chorioretinopathy. Much is now known about the genetics of these enzymes and how genetic variants alter their function, but how these variants contribute to disease remains largely unresolved. Here we discuss what is known about their structure and function and highlight some of the knowledge gaps that affect development of drugs targeting these enzymes.
M1 氨肽酶家族的内肽酶亚家族在加工和修剪 MHC I 类分子呈递的肽中起着重要作用。几项大规模基因组研究已经确定了该酶家族的成员（尤其是 ERAP1 和 ERAP2）与免疫介导的疾病之间的关联，包括强直性脊柱炎、银屑病和鸟枪弹样脉络膜视网膜病变。现在已经了解了这些酶的遗传学以及遗传变异如何改变它们的功能，但这些变异如何导致疾病在很大程度上仍未得到解决。本文讨论了它们的结构和功能，并强调了一些影响针对这些酶的药物开发的知识空白。
